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学科主题: 基础医学
题名:
High glucose stimulates GRO secretion from rat microglia via ROS, PKC, and NF-kappa B pathways
作者: Quan, Yi; Du, Jianhai; Wang, Xian
关键词: high glucose ; microglia ; GRO ; ROS ; PKC ; NF-kappa B
刊名: JOURNAL OF NEUROSCIENCE RESEARCH
发表日期: 2007-11-01
DOI: 10.1002/jnr.21421
卷: 85, 期:14, 页:3150-3159
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Neurosciences
研究领域[WOS]: Neurosciences & Neurology
关键词[WOS]: CENTRAL-NERVOUS-SYSTEM ; HUMAN ENDOTHELIAL-CELLS ; OXIDATIVE STRESS ; GENE-EXPRESSION ; C-PEPTIDE ; DIABETIC-RETINOPATHY ; CYTOKINE PRODUCTION ; SIGNALING PATHWAYS ; INTERLEUKIN-8 ; HYPERGLYCEMIA
英文摘要:

Hyperglycemia causes direct neuronal damage in diabetic encephalopathy. Microglia have been found to be activated in diabetic encephalopathy, presumably mediating and amplifying neuron degeneration. Chemokine IL-8 plays an important role in the pathogenesis of encephalopathy. Therefore, we investigated whether high glucose could activate microglia and stimulate IL-8 secretion and if so, the possible mechanisms that were involved. ELISA results showed that treatment with high glucose (35 mM) compared with treatment with low glucose (10 mM) time-dependently elevated secretion of GRO (the rat ortholog of human IL-8) in primary cultured rat microglia. Real-time PCR results showed GRO mRNA expression also increased in response to high glucose in a time-dependent manner. These effects were specific to high glucose because the osmolality control had no such effect. High-glucose treatment stimulated the formation of ROS, as seen in the DCF fluorescence assay, increased phosphorylation of PKC, as seen in the Western blot analysis, and activated NF-kappa B, as seen in the luciferase reporter assay. In addition, treatment with the ROS scavenger NAC (2 mM) significantly reduced the high glucose-induced phosphorylation of PKC and GRO secretion. Treatment with the PKC activator PMA (10-50 nM) stimulated GRO secretion, and the PKC inhibitors calphostin C (300 nM) or chelerythrine (1 mu M) attenuated the high glucose-induced GRO secretion. Furthermore, the NF-kappa B inhibitors MG132 (10 mu M) or PDTC (5 mu M) completely blocked the high glucose-induced GRO secretion. In conclusion, high glucose induces GRO secretion and mRNA expression in activated rat microglia, which is mediated by the ROS, PKC, and NF-kappa B pathways. High glucose-induced IL-8 production by microglia may contribute to diabetic encephalopathy. (c) 2007 Wiley-Liss, Inc.

语种: 英语
WOS记录号: WOS:000250970100017
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/56300
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Peking Univ, Dept Physiol & Pathophysiol, Sch Basic Med Sci, Beijing 100083, Peoples R China
2.Peking Univ, Hosp 3, Minist Educ, Key Lab Mol Cardiovasc Sci,Inst Vasc Med, Beijing 100871, Peoples R China

Recommended Citation:
Quan, Yi,Du, Jianhai,Wang, Xian. High glucose stimulates GRO secretion from rat microglia via ROS, PKC, and NF-kappa B pathways[J]. JOURNAL OF NEUROSCIENCE RESEARCH,2007,85(14):3150-3159.
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